Found two new strategies to cure psoriasis

28 04 2014

Experiments in mice and samples from patients suggest that to combat psoriasis, it is possible to act with commercial drugs without side effects just. The works are collected in the prestigious journals Immunity and Science Translational Medicine.

 

Almost ten years ago, the group led by Erwin Wagner, currently at the Centro Nacional de Investigaciones Oncológicas (CNIO), generated unexpectedly, as a result of basic research work, a mouse genetically modified with symptoms very similar to the psoriasis.

After he published the finding in Nature, the researchers decided to use this mouse model to study the molecular mechanisms that underlie the development of this disease, and look for innovative and efficient therapies.

Now, the same group has discovered two possible new treatment avenues, based on pharmacological compounds that already exist and which, in mice, they do not seem to have side effects.

These new strategies are the result of in-depth studies on the biology of the disease, he unveiled some of its causal agents. Like this, routes of treatment studied Act on these agents.

Epidermis humana transplantada en ratón con signos de psoriasis (izquierda) y sin alteraciones cuando se trata con bloqueantes del microRNA miR-21 (derecha). / CNIO

Human skin transplanted in mice with signs of psoriasis (left) and without alterations when dealing with blockers of the microRNA miR-21 (right). / CNIO

 

In one of the works, published in December in the journalImmunity, It is shown that by blocking a protein called S100A9 disease symptoms disappear. In another publication, He published this weekScience Translational Medicine, They show that this also happens if it acts on a non-coding RNA, the micro-RNA, miR-21.

As they write in the first study Helia B. Schönthaler and colleagues, "the last decade biological therapies have proven to be effective against inflammatory diseases. However, These treatments generate concern about long-term side effects involving a possible increased risk of infection and cancer".

Therefore, Add the authors, "the development of effective drugs without these side effects and applicable locally it would be beneficial for patients with psoriasis". In particular, inhibitory S100A9 strategies "have a great potential of becoming new effective treatments against psoriasis".

On the other hand, in the last article, with Juan Guinea-Viniegra as first signer, It is claimed that "block miR-21 could offer advantages over existing treatments since the obtained efficiency is the same, but the side effects are probably reduced"and highlights that mice and samples of patients transplanted mice in which this strategy has been tried"show a therapeutically relevant improvement".

Schönthaler and Guinea-Viniegra belong to the Group of Wagner, Director of the program of biology cell of Cancer Foundation BBVA-CNIO. Both researchers are involved in the two works.

 

Identify the important mutations

For authors, that the two investigations aimed at completely different targets reveals the complex and heterogeneous psoriasis, a disease that involves many factors (EPI)genetic and environmental - and for which until recently animal models - there were no.

One of the successes of these works is that they manage to identify some of the key changes, and also give clues about its relationship with others already found. For example, in the animal model presented in 2005 by this group, psoriasis symptoms occur when two genes are removed in the mouse epidermis; they are just a few, but they regulate the expression of many other genes.

Now Guinea-Viniegra and Schönthaler affirm not only that "should have" a relationship between the two strategies that they have tested, but also with the genes altered in the model of 2005.

"Have been described hundreds of genes increased or decreased in psoriasis, but only few of them - tens - know that they can be the cause of the disease", explain. "We have described two new genes/proteins that known to be increased in psoriasis, and we now demonstrate that they have a causal role in disease".

Sophisticated molecular biology techniques have been used in both works, and human samples. In the study led by Schönthaler, the first step was to compare skin lesions of psoriasis with healthy skin.

To do this, working in collaboration with the Group of Esteban Daudén, in the Hospital Princess, in Madrid, they obtained samples of 19 the type of most common psoriasis patients, and they analyzed the proteins present in your skin.

They identified 1.217 proteins, of which 214 they were in significantly different quantities in healthy skin and lesions. In particular, the complex of proteins S100A8-S100A9 was much more abundant in psoriasis.

 

Already with that track, the researchers studied the importance of S100A8-S100A9 creating a mouse that this protein is missing. And the result was that the symptoms of psoriasis disappeared. Researchers also analyzed the proteins on which acts S100A8-S100A9, and so they have also unveiled other possible targets.

But the second good news of this work is that it demonstrates that a drug that is already on the market - is used for prostate cancer and prevent rejection in transplants - blocks S100A9, and should be effective against psoriasis. "That doesn't mean that I will be already approve its use in psoriasis, but it greatly facilitates the process because it is a known drug, We know that it is safe", designates Schönthaler.

 

Mice with human skin

The work led by Guinea-Viniegra explores another level of information stored in the DNA encoding: the microRNAs. Discovered just two decades ago, and without that is known even in detail its function or its role in diseases, the microRNAs are small fragments of nucleic acid that are not translated into proteins, but they still regulate the expression of other genes.

In the case of psoriasis, It was already known that the microRNA miR-21 was much more abundant than usual. Like this, to investigate their role researchers inhibited miR-21 in their mouse model, and they observed as symptoms disappear in a short time and without apparent side effects.

The next thing was to work with human samples. The authors of the work grafted skin from a dozen of patients samples in living mice - a strategy of xenotransplantation which studies the reaction of a human tissue in vivo without endangering the person-, and they were locally treated lesions with a compound that blocked miR-21.

"The results have been very positive and are encouraging, Since this would be a totally innovative way of treating psoriasis", concludes Guinea-Viniegra.

 

 

On psoriasis

Psoriasis affects to until the 3% of the world's population, and can alter the quality of life of severe form. Its cause is not known and today doesn't heal completely. The goal is to give very effective but non-toxic treatments.

The latest generation of drugs developed against it, biological apodadas agents, are considered a breakthrough, but apply only during periods limited by the seriousness of their side effects - can be generated from other forms of psoriasis, tuberculosis or leukemia-.

 

 

Bibliographic reference:

S100A8-S100A9 protein complex mediates psoriasis by regulating the expression of complement factor C3. Schönthaler HB, Guinea-Viniegra J, Wculek SK, Ruppen I, Ximénez-Embún P, Guio-Carrion A, R Navarro, N Hogg, Ashman K, Wagner EF. Immunity (2013). DOI: 10.1016/j.immuni.2013.11.011

Targeting miR-21 to treat psoriasis. John Guinea-Viniegra, Maria Jimenez, Helia B. Schönthaler, Raquel Navarro, Yolanda Delgado, Maria Jose Concha-garzon, Erwin Tschachler, Susanna Obad, Esteban Dauden, Erwin F. Wagner. Science Translational Medicine (2014). DOI: 10.1126/scitranslmed.3008089

The works have been funded by the BBVA Foundation, the Ministry of economy and competitiveness and the European Union.

 

 

 

Agenciasinc.es [en línea] Madrid (ESP): agenciasinc.es, 28 April of 2014 [REF. 26 de febrero de 2014] Available on Internet: http://Noticias/Encontradas-dos-nuevas-estrategias-para-curar-la-psoriasis www.agenciasinc.es/



Doctors and engineers design a new thrombectomy device

24 04 2014

The UPM researchers collaborate with British doctors in the design and optimization of a device aimed at the Elimination of clogged arteries more safely.

 

The Railway Technology Research Center (ICR) of the Polytechnic University of Madrid (UPM), one of whose lines of work is the use of different techniques of simulation in multi-domain systems, He is working on the improvement of a device for the extraction of clots by means of absorption that can function effectively without causing possible strokes by the break of the clot. The work is done in collaboration with a medical team of United Kingdom, where are the laboratory tests for the modeling and characterization of the device carried out.

A stroke occurs when the blood flow to a part of the brain is stopped; in the event of an arrest for more than a few seconds, the brain cannot receive blood and oxygen, causing permanent damage. According to the World Health Organization (WHO), more than 15 millions of people die in the world because of brain vascular diseases. In particular, cerebrovascular accidents represent one of the leading causes of death and the leading cause of disability in adults, being one of the neurological pathologies of greater social impact, with more than 120.000 new cases each year in Spain.

Treatments for this type of accident can be divided in chemical agents and mechanical thrombectomy devices. Any mechanical device for extraction purposes can be summarized to make removal of the clot formed on the inside of the arteries and restore blood flow in the artery. Numerous devices have been developed for years, many of them operate on the periphery of the vascular system; However, There are relatively few who have been employed in the cerebral vasculature. One of the main problems of these devices is that it can cause embolism downstream or rupture of artery walls due to its moving parts.

 

 

The development of new devices that allow to effectively remove the presence of these clots is supported by the high percentage of population affected and the different existing risks, Noting the possibility of designing a device based on absorption, no moving parts and a simple design, that it can function as an effective exhaust of clots without causing possible strokes due to breakage of the clot.

The new extraction device being developed is based on the trombectomico device by absorption called GP, invented in United Kingdom, that it has no moving parts. Taking as starting point the initial and according to British medical equipment design, researchers from the ICR are proceeding to the introduction of improvements and optimization through the use of different simulation techniques, for which he is working on modelling and characterization of the medical device from laboratory tests carried out in United Kingdom. In this way, He is working on the optimization of the geometry of the device, in the estimation of the optimal range of pressures to different situations and characteristics of the clot, en la distribución del flujo en el entorno del mismo y en el proceso de eliminación del coágulo de la pared arterial.

 

ROMERO, G; HIGUERA, I; MARTÍNEZ, ML; PEARCE, G; PERKINSON, N; ROOM, (C); WONG, J. "Computational Modeling of a New Thrombectomy Device for the Extraction of Blood Clots". Advances in Experimental Medicine and Biology, Vol. 680. 2010. DOI: 10.1007/978-1-4419-5913-3_69

PEARCE, G; BROOKER, L; MIRZA, N; JONES, T; ROOM, (C); WONG, J; PERKINSON,NN; ROMERO,GG; MARTINEZ, ML; HIGUERA, I. "Bond graph modeling of the in vitro performance of the GP thrombectomy Device in combination with local delivery of alteplase". International Journal of Stroke, Vol. 5(see). 2010. DOI: 10.1111/j. 1747-4949.2010.00492. x

ROMERO, G; MARTÍNEZ, ML; MAROTO, J; FÉLEZ, J. "Blood Clot Simulation Model by Using the Bond-Graph Technique". The Scientific World Journal , Volume 2013. DOI: 10.1155/2013/519047

ROMERO, G; MARTÍNEZ, ML; PEARCE, G; WONG, J. "Analysis of the GPATD: Geometrical Influence on Blood Clot Extraction Using CFD Simulation ". UkSim-AMS 16th International Conference on Modeling and Simulation. 26-28 March 2014. Cambridge (UK).

 

Enlaces de interés:

"The ‘ GP’ Mechanical Thrombectomy Device ". Journal of Stroke and Cerebrovascular Diseases 18(4), 2009, pp. 288-293.

 

 

 

Upm.es [en línea] Madrid (ESP): upm.es, 24 de abril de 2014 [REF. 07 April of 2014] Available on Internet: http://www.upm.es/institucional/UPM/CanalUPM/Noticias/2d168776be125410VgnVCM10000009c7648aRCRD



European study reveals new causes of mouth and throat cancer

21 04 2014

Poor oral health and failure to have regular dental checks could increase the risk of mouth and throat cancer, according to a pan-European study.

The research also suggests – based on a small number of tumour patients – that excessive use of mouthwash may also cause this particular form of cancer. Excessive use is defined as more than three times a day.

It has been established for some time that smoking and heavy alcohol consumption, particularly in combination, are strongly related to mouth and throat cancers. Low socio-economic status is also recognised as a contributory factor.

Now, however, a new study carried out by researchers at the University of Glasgow Dental School – as part of a Europe-wide collaboration co-ordinated by the International Agency for Research on Cancer and led by the Leibniz Institute for Prevention Research and Epidemiology – BIPS in Bremen, Germany – has identified new risk factors for upper aerodigestive tract cancer (cancer of the mouth, larynx, pharynx and esophagus).

The study of 1,962 patients with mouth and throat cancers, with a further 1,993 people used as comparison control subjects, was conducted in 13 centres across nine countries and supported by EU funding.

Prof. Wolfgang Ahrens, Deputy Director of the BIPS, said: "These results are really important. Up until now, it was not really known if these dental risk factors were independent of the well known risks for mouth and throat cancers – smoking, alcohol and low socioeconomic status. "

The researchers were able to strip out the causation factors of smoking, alcohol and socio-economic factors, and still found there was a connection between poor oral health and increased risk of mouth and throat cancers.

The findings are highly "nuanced" and there is an interconnectedness of many of the risk factors, he stressed, but there was now evidence that poor oral health and poor dental care were also part of the picture.

The definition of poor oral health included people who had complete or part dentures, people with persistently bleeding gums.

"People should not assume that if they wear dentures and have none of their own teeth left, they have no need to see a dentist,"said Dr David Conway, Clinical Senior Lecturer at the University of Glasgow Dental School and one of the senior authors of the study. "On the contrary, even if you have got dentures, you should make sure you go for regular check-ups,” he said.

People with poor dental care were defined as those who hardly ever or never brushed their teeth or visited the dentist. The frequency of dental visits should be determined by a dentist's risk assessment and if people fell into the low risk category it could be once a year or even every two years, said Dr Conway.

"It is not a case of ' one size fits all '. Visits could be six-monthly, but certainly not five-yearly,” Dr. Conway added.

The possible role of mouthwash as a causative factor would require further research, said Professor Ahrens. There might be a relationship between excessive use of mouthwash and people who used it to mask the smell of smoking and alcohol. Nevertheless, the researchers found that "frequent use of mouthwashes (3-plus times per day) was associated with an elevated risk of developing mouth and throat cancer ", although they were unable to analyse the types of mouthwash used many years ago by participants in the study.

Dr Conway said: "I would not advise routine use of mouthwash, full stop. There are occasions and conditions for which a dentist could prescribe a mouthwash – it could be that a patient has a low salivary flow because of a particular condition or medicine they are taking. But for me, all thats necessary in general is good regular brushing with a fluoride toothpaste and flossing combined with regular check-ups by a dentist. "

The research group, which includes collaborators from Germany, UK, Estonia, Switzerland, Greece, the Czech Republic, Italy, Norway, Spain, USA, Croatia, Ireland and France, have recently received a new tranche of funding from the EU and Who is International Agency for Research of Cancer, which will be used to research prognostic factors as well as risk factors.

 

 

Find out more:

 

Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE (Alcohol-Related Cancers and Genetic-susceptibility in Europe) study. Wolfgang Ahrens; Hermann Pohlabeln; Ronja Foraita; Mari Nellis; Pagona Lagiou;Art Lagiou; Christine Bouchardy; Alena Slamova; Miriam Schejbalova; Franco Merletti; Lorenzo Richiardi; Kristina Kjaerheim; Antonio Agudo; Xavier Castellsague; Tatiana Macfarlane; Gary J Macfarlane; Yuan-Ching Amy Lee; Renato Talamini; Luigi Barzan; Cristina Canova; Lorenzo Simonato; Peter Thomson; Patricia McKinney; Alex D McMahon; Ariana Znaor; Claire M Healy; Bernard E Mccarthy; Andres Metspalu; Manuela Marron; Mia Hashibe; David I Conway; Paul Brennan.

 

Published in Oral Oncology http://www.oraloncology.com/article/PIIS1368837514000657/abstract

 

 

Gla.ac.uk [en línea] Glasgow (UK): gla.ac.uk, 21 de abril de 2014 [REF. 04 April of 2014] Available on Internet: http://www.gla.ac.uk/news/headline_320819_en.html



Tamiflu: an analysis of all the data

17 04 2014

Was the government right to spend half a billion pounds in stockpiling the antiviral drugs Tamiflu and Relenza in preparation for a flu pandemic?

These drugs were handed out via a phoneline during the swine flu pandemic of 2009 as part of a wider public health strategy.

Professor Carl Heneghan of Oxford University’ s Department of Primary Care Health Sciences and colleagues in the independent Cochrane Collaboration are clear that the money was wasted. They argue that the decision to stockpile the drugs might have been different had we had access to all the clinical data on their effectiveness.

Now we do have that evidence, and Carl says: ‘ There is no credible way these drugs could prevent a pandemic.’ Speaking at a media briefing at the Science Media Centre in London, he said the money spent on stockpiling had been ‘ thrown down the drain’.

Since 2009, the Cochrane researchers have had a long running battle with the drug firms that manufacture Tamiflu and Relenza (Roche and GSK, respectively) to get unconditional access to their full data. They finally received everything last year, after first GSK then Roche said they would provide the materials – a significant development in the campaign to increase openness and accessibility of complete trial data.

The Cochrane group has been significant players, along with the AllTrials campaign, the BMJ medical journal, Ben Goldacre and others, in changing the whole approach to this issue among researchers, journals, drug firms and regulators. The simple argument is that if we are to make the right decision on what are the best drugs – considering their safety, effectiveness and the balance of benefits they offer in treating conditions over their side-effects – we need to have all the evidence available.

The researchers have now made that assessment for Tamiflu in the prevention and treatment of flu. They have reviewed a phenomenal amount of material, and with the BMJ and the Cochrane Collaboration, have published their conclusions today. They call on government and health policy decision makers to review guidance on the use of Tamiflu in light of their new evidence.

They found that Tamiflu is effective – but it shortens symptoms of flu by only around half a day on average. And importantly, they say, there is no good evidence to support claims that it reduces complications of influenza or admissions to hospital.

Then there are the side effects. Using Tamiflu to treat flu, the evidence confirms an increased risk of suffering from nausea and vomiting.

When Tamiflu is used to prevent flu, the drug can reduce the risk of people suffering symptomatic influenza. But there was an increased risk of headaches, psychiatric disturbances, and kidney events.

The review authors, Drs Tom Jefferson, Carl Heneghan and Peter Doshi, conclude that there are insufficient grounds to support the stockpiling of Tamiflu for mass use in a pandemic. From the best conducted randomised trials, there just isn't enough evidence on the crucial elements of reducing serious complications of flu that can lead to hospitalisation and death, and the prevention of spread of flu. On the other hand we know there would be side-effects.

Not all scientists agree on the assessment of the balance of benefits of these antivirals versus their side-effects. Virologist Professor Wendy Barclay at Imperial College London believes the shorter time that symptoms last is important: ‘ Although one day does not sound like a lot, in a disease that lasts only 6 days, it is...We have only two drugs with which we can currently treat influenza patients and there is some data to suggest they can save lives. It would be awful if, in trying to make a point about the way clinical trials are conducted and reported, the review ended up discouraging doctors from using the only effective anti-influenza drugs we currently have.’

Roche, the manufacturers of Tamiflu, fundamentally disagree with the overall conclusions of the Cochrane review and criticised some of the report methodology. In media reports, UK Medical Director Dr Daniel Thurley has said: ‘ Roche stands behind the wealth of data for Tamiflu and the decisions of public health agencies worldwide, including the US and European Centres for Disease Control & Prevention and the World Health Organization.’

Indeed, Roche have pointed to a large observational trial in the Lancet Respiratory Medicine that they funded which recently reported a reduction in deaths among those hospitalised with swine flu H1N1, though there are some who disagree with that analysis to.

So what to make of all of this? An editorial in the Guardian concludes: ‘ The only way to resolve the argument is proper science. That means transforming clinical trials, harmonising the way they are carried out. It has happened with malaria drugs, and it is happening with HIV. The industry must allow access to their data. Confident that like is compared with like, trials can then be subjected to meta-analysis, allowing statisticians to drill down into sub-populations to establish when a drug performs most effectively.’

The editorial points to the need to be able to react swiftly and carry out good research actually during pandemics, as former Oxford University professor and now director of the Wellcome Trust, Jeremy Farrar, argued in the paper last month.

What has really changed is the ability to have these discussions based on all of the evidence. There is a real shift in the level of scrutiny and the analyses that are now possible with access to all clinical trial data (although dealing with all these reams of data also brings new challenges to). That is a phenomenal change and a real achievement by the Cochrane researchers.

David Spiegelhalter, Winton Professor of the Public Understanding of Risk at the University of Cambridge, comments: ‘ This is a ground-breaking review. Since important studies have never been published, the reviewers have had to go back to clinical trial reports comprising over 100,000 pages: the effort to obtain these is a saga in itself. The poor quality of these reports clearly made extracting relevant data a massive struggle, with many pragmatic assumptions having to be made, but the final statistical methods are standard and have been used in hundreds of Cochrane reviews. Let's hope that in future high-quality data can be routinely obtained and this type of review becomes unnecessary.’

By Jonathan Wood

 

Ox.ac.uk [en línea] Oxford (UK): ox.ac.uk, 17 de abril de 2014 [REF. 10 April of 2014] Available on Internet: http://www.ox.ac.uk/media/science_blog/140410.html



A biocomputacional platform will analyze cancer cells and bacteria

14 04 2014

Useful to be able to predict the behavior that will follow the cancer cells and bacteria to a specific treatment

Scientists from the University of Costa Rica (UCR) they will create a platform biocomputacional quickly processed all information from investigations that try to fight the cancer chemotherapy cells and bacteria resistance to antibiotics.

 

El investigador principal del proyecto es el Dr. Francisco Siles Canales, coordinador del Laboratorio de Investigación en Reconocimiento de Patrones y Sistemas Inteligentes. FOTO: UCR.

The principal investigator for the project is Dr. Francisco Siles channels, Coordinator of the research laboratory on pattern recognition and intelligent systems. PHOTO: UCR.

 

In the fight of cancer cells and bacteria scientists encounter the problem that these infectious agents are resistant to therapies that apply to remove them and cure the evil. in the case of cancer cells, they possess blameable mechanisms that make that some survive chemotherapy even if they are damaged in their deoxyribonucleic acid (ADN).

The bacteria become resistant to antibiotics that are facing, so you constantly have to be creating new and more powerful.

To be able to predict the behavior that will follow the cancer cells and bacteria to a specific treatment, It is necessary to process a vast amount of information, which requires a powerful computer processing capacity.

This resource is what is proposed by the interdisciplinary team of scientists grouped in the network of research on Biocomputation (RIB), discipline that it applies computational methods, mathematical and engineering to biological problems.

The principal investigator for the project is Dr. Francisco Siles channels, Coordinator of the research laboratory on pattern recognition and intelligent systems (PRIS-Lab) School of electrical engineering of the University of Costa Rica (UCR).

They also involved researchers from the school of Microbiology and the tropical diseases research centre (ICLS) UCR. Also researchers from the school of public health and the Centre for research in information technology and communication (CITIC).

 

Math, cells and bacteria

Dr. Siles said that this multidisciplinary team is avocado to "build a mathematical model that describes the defensive process to treatments by these agents that cause diseases, then implement it on the computer".

"It is to say that it is not as a theoretical model, but this theoretical model to implement it and that we can validate it experimentally with colleagues in microbiology. We propose the analytical model, We simulate in the computer, "we took him to the lab and see that as is true and what go wrong coming out will adjust it."

To check the effectiveness of the predictions of the mathematical model must initially work with lines of bacteria and cancer cells which are widely studied and which has lots of information.

About the cells, one of the members of the multidisciplinary team, Steve Quiros Barrantes microbiologist, He said that they will "work with cancer lines that are highly studied, of which the details are very well known and are very well described, because they have been many years of analysis by the scientific community."

He explained that this information will be used to develop the platform and check if the mathematical model manages to correctly predict the behaviour of certain cancer cells growing to apply to him any specific chemotherapy.

If it is confirmed in the laboratory that the evolution of the cell is equal to that predicted the biocomputacional platform, You can then be applied to predict the behavior of other cells or bacteria in study.

The project is called"Platform biocomputacional for genomic data analysis to overcome resistance to cancer therapy and microbial infections”. At the end of the 2013 He won the Fund of incentives given annually by the Ministry of science, Technology and telecommunications (MICITT).

Dr. Siles also coordinates the research network in scientific computing, also created by the UCR researchers in collaboration with the national Collaboratory for advanced computing (CNCA), National Center of high-tech (CeNAT), as well as also other centres and research laboratories Costa Ricans and foreigners.

 

 

Dicyt.com [en línea] Salamanca (ESP): dicyt.com, 14 de abril de 2014 [REF. 11 April of 2014] Available on Internet: http://noticias/una-plataforma-biocomputacional-analizara-celulas-cancerosas-y-bacterias www.dicyt.com/



Artificial Organs May Finally Get a Blood Supply

10 04 2014

Artificial tissue has always lacked a key ingredient: blood vessels. A new 3-D printing technique seems poised to change that.

 

Living layers: Harvard researchers demonstrate their method for creating vascularized tissue constructs by printing cell-laden inks in a layered zig-zag pattern.

Living layers: Harvard researchers demonstrate their method for creating vascularized tissue constructs by printing cell-laden inks in a layered zig-zag pattern.

In what may be a critical breakthrough for creating artificial organs, Harvard researchers say they have created tissue interlaced with blood vessels.

Using a custom-built four-head 3-D printer and a "disappearing" ink, materials scientist Jennifer Lewis and her team created a patch of tissue containing skin cells and biological structural material interwoven with blood-vessel-like structures. Reported by the team in Advanced Materials, the tissue is the first made through 3-D printing to include potentially functional blood vessels embedded among multiple, patterned cell types.

In recent years, researchers have made impressive progress in building tissues and organ-like structures in the lab. Thin artificial tissues, such as a trachea grown from a patient's own cells, are already being used to treat patients (see "Manufacturing Organs”). In other more preliminary examples, scientists have shown that specific culture conditions can push stem cells to grow into self-organized structures resembling a developing brain, a bit of a liver, or part of an eye (see "Researchers Grow 3-D Human Brain Tissues,” “A Rudimentary Liver Is Grown from Stem Cells,"and"Growing Eyeballs”). But no matter the method of construction, all regenerative projects have run up against the same wall when trying to build thicker and more complex tissues: a lack of blood vessels.

Lewis's group solved the problem by creating hollow, tube-like structures within a mesh of printed cells using an "ink" that liquefies as it cools. The tissue is built by the 3-D printer in layers. A gelatin-based ink acts as extracellular matrix—the structural mix of proteins and other biological molecules that surrounds cells in the body. Two other inks contained the gelatin material and either mouse or human skin cells. All these inks are viscous enough to maintain their structure after being laid down by the printer.

A third ink with counterintuitive behavior helped the team create the hollow tubes. This ink has a Jell-O-like consistency at room temperature, but when cooled it liquefies. The team printed tracks of this ink amongst the others. After chilling the patch of printed tissue, the researchers applied a light vacuum to remove the special ink, leaving behind empty channels within the structure. Then cells that normally line blood vessels in the body can be infused into the channels.

 

Building actual replacement tissues or organs for patients is a distant goal, but one the team is already weighing. "We think it's a very foundational step, and we think it's going to be essential toward organ printing or regeneration,"says Lewis, who is member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The smallest channels printed were about 75 micrometers in diameter, which is much larger than the tiny capillaries that exchange nutrients and waste throughout the body. The hope is that the 3-D printing method will set the overall architecture of blood vessels within artificial tissue and then smaller blood vessels will develop along with the rest of the tissue. "We view this as a method to print the larger vessels; then we want to harness biology to do the rest of the work,"says Lewis.

 

 

By Susan Young Rojahn

 

Technologyreview.com [en línea] Cambridge, MA (USA): technologyreview.com, 10 April of 2014 [REF. 06 March of 2014] Available on Internet: http://www.technologyreview.com/news/525161/artificial-organs-may-finally-get-a-blood-supply/



Observing behavior of single molecules in real time

7 04 2014

Stanford scientists develop technique for observing behavior of single molecules in real time

The new technique allows scientists to observe single molecules of protein or DNA as they bind with other molecules, and could lead to better drug designs.

 

Nearly every biological or chemical reaction that makes life possible involves single molecules interacting in the watery solution that sloshes in and around cells.

Now, a Stanford chemistry professor and his graduate student have developed a technique for observing these processes as they happen in real time.

WHATEVER. Moerner, a professor of chemistry, specializes in single molecule fluorescence, a field that involves studying how biomolecules – such as DNA and enzymes – work in cells to carry out the processes that are critical to life. The new advance describes how Moerner and his graduate student, Quan Wang, modified an ABEL (Anti-Brownian ELectrokinetic) trap, a machine invented in Moerner’ s lab that uses electric fields to manipulate individual small molecules from the light they emit, to isolate a single strand of DNA and observe how it binds to other DNA, in aqueous solution.

 

Stanford researchers have developed a technique to observe behavior of single molecules of protein or DNA in real time.

Stanford researchers have developed a technique to observe behavior of single molecules of protein or DNA in real time.

The work is detailed in the journal Nature Methods.

Getting this process started takes a little bit of luck, Wang said, as they must wait until a single molecule happens to be in the vicinity of the trap. This all happens at an incredibly tiny scale. The trap covers about a square centimeter, but the molecules are just 1 nanometer long. (For perspective, that’ s trapping a single grain of pollen on a football field, and then, without ever touching it, studying its behavior and characteristics.)

Once a lone molecule has entered the trap, its motion comes under continuous surveillance. Although the molecule doesn’ t want to sit still, every time it attempts to escape, the ABEL trap automatically applies electric fields to push it back.

Using physical analysis and computational tricks from machine learning, Wang developed an algorithm to convert the observed single-molecule motions inside the trap into information about the molecule’ s size and electric charge. From this, the researchers can determine whether the target molecule has interacted with another molecule.

In the case of DNA, if it begins to hybridize – that is, if it begins to bond to a complementary strand of DNA – the readings from the trap will show that the trapped DNA has an increase in both size and charge. When the process reverses a few instants later – that is, when the DNA melts and its complementary strand falls off – the trapped molecule’ s size and charge change back correspondingly.

“It is really quite amazing to be able to trap a single short piece of single-stranded DNA, to watch it for many seconds and directly observe a partner strand bind and unbind,” Moerner said. “This is really an essential process.”

The researchers conducted similar tests using proteins, and Wang said that the technology in its current state can easily be applied to many different types of molecules to study other binding processes.

“We’ ve done the proof of concept for the method, and soon we want to apply it to two very specific problems and get some science out of it,” said Wang, who is a graduate student in electrical engineering.

The first involves drug design. Drugs target diseases by binding to receptor molecules on cells, and the drug’ s effectiveness often depends on how well and for how long it binds to its receptor. By gauging the size and total charge of the molecules as they form a complex, the trap can directly measure how long it takes for the drug to find its receptor and how long the complex stays together. This information could guide scientists toward designing drugs that better match their target receptor.

Another application is to study the role protein aggregation plays in various diseases. As people age, proteins can become “sticky” and accumulate, a hallmark of several diseases, including Huntington’ s. The trap provides a direct way to study the size distribution of these proteins and how they aggregate; understanding this effect could lead to treatments that inhibit it.

Other students and postdoctoral scholars in Moerner’ s group are working to make the trap respond even more quickly, to perform more optimally in other situations, or to study different properties of single molecules. Moerner said that the interdisciplinary makeup of his group (including him; he holds a degree in electrical engineering as well as in chemistry) is critical for understanding all the different facets of this work, and then for smart implementation of it.

“We use light to probe molecules – that’ s physics and chemistry,” Moerner said. “And we apply it to biology and biomedical systems. But at the core is precise measurement, extracting as much information as possible from a single object, and that can be done with concepts from electrical engineering.

“It’ s a natural thing at Stanford for students in one department to do thesis research in another. It’ s one of the wonderful aspects at Stanford, and it can lead to wonderful work such as this.”

 

BY BJORN CAREY

 

 

News.stanford.edu [en línea] Stanford, CA (USA): news.stanford.edu, 07 April of 2014 [REF. 14 March of 2014] Available on Internet: http://news.stanford.edu/news/2014/march/dna-binding-observed-031414.HTML

 



Ayudando al cerebro a autoregenerarse

3 04 2014

A new strategy in regenerative medicine can promote recovery from brain injury

 

Researchers at the Institute for bioengineering of Catalonia tissue regeneration (IBEC), at the University of Barcelona (UB) and the Polytechnic University of Catalonia (UPC) they have developed an implant that it stimulates the regeneration of brain tissue, especially in cases of injury pre- and postnatal.

 

Imagen: Andamios de nanofibras aleatorias (izquierda) y alineadas (derecha) tras una semana de la implantación en el córtex cerebral de ratones. Las células gliales (verde) y los vasos sanguíneos (rojo) penetran en el andamio alineado y no en las fibras aleatorias (rayas blancas).

Image: Random nanofibers scaffolds (left) and aligned (right) After a week of implantation in the cerebral cortex of mice. Glial cells (Green) and the blood vessels (Red) they penetrate aligned scaffold and not random fibres (white stripes).

 

In the study, led by the Dra. Soledad Alcántara of the Neural development of the UB Group, scientists have discovered that these implants biodegradable polylactic acid nanofibers facts (PLA) they reproduce some aspects of the natural environment of the embryonic brain and stimulate tissue regeneration.

These implants, tissue engineering known as “scaffolding”, free l-lactate, a molecule that acts as a common cell phone signal to induce angiogenesis (formation of new blood vessels). They also reproduce the neurogenic niche, that is to say, the environment in which the neural progenitors generate new neurons and glial cells, that you migrate following migration patterns that occur during brain development.

"Brain lesions are the common cause of many disabilities, due to the loss of nervous tissue and the formation of cavities that inhibit the growth of neurons", said Zaida Álvarez member of the Group of biomaterials for regenerative therapies of IBEC and the Neural development of the UB and first author of the article group. "To find effective regenerative strategies that promote the recovery of the brain after traumatic injury we have to focus on resolving current bottlenecks: "the weak integration of the implant and cell survival."

When was designed in the IBEC PLA scaffold implanted into newborn mice, the lactate released during degradation acted as a source of alternative energy encouraging the growth of neurons and activating the endogenous progenitors. The fibers used to construct the “structure” they reproduced the natural organization in 3D, as well as the topology of the embryonic radial glia, which favored the vascularization and neuronal migration during brain growth.

"Through improvement of implants has been possible to regulate the bio-physical and metabolic parameters that lead the restoration of the function of the nervous tissue after an injury", without the need for exogenous cells, growth factors or genetic manipulation,"said Zaida Álvarez. "Although there is still a long way to go until these experiments can translate to the clinic - we have to see if there is a similar regenerative response in adult mice - our results open up a hopeful and exciting perspectives in the design of cell-free Implantable devices."

 

Article by reference: Alvarez, Z., Brown, O., Castells, A.A., Mateos-Timoneda, M.A., Planell, J.A., Engel, E. & Alcantara, S. (2014). Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold. Biomaterials, 35, 17, 4769–4781

 

 

Ibecbarcelona.eu [en línea] Barcelona (ESP): ibecbarcelona.EU, 03 April of 2014 [REF. 25 March of 2014] Available on Internet: http://www.ibecbarcelona.eu/NOTICIAS-DE-INVESTIGACION/helping-the-brain-rebuild-itself.html